Pattern of bloodstream infections in patients with hematological malignancies in a tertiary care centre.

BACKGROUND: The purpose of our study was to evaluate the clinical characteristics, to understand the pattern of bloodstream infections (BSIs), and to determine the risk factors contributing to high‑risk febrile neutropenia in patients with hematological malignancy. MATERIALS AND METHODS: A comprehensive review of retrospective data was done from 2004 till 2012 from a single center. RESULTS: There were total 171 consecutive febrile episodes with 103 acute lymphoblastic leukemia (ALL) patients and 63 acute myeloid leukemia (AML) patients. The highest number of febrile neutropenia episodes occurred during ALL and AML induction followed by consolidation treatment with high‑dose cytarabine. In our study population, the most common organisms isolated were Gram‑positive (20%) followed by Gram‑negative (6.4%) organisms. The incidence of fungal sepsis was only 3%. In our study, it was seen that the recovery from febrile neutropenia depends upon the disease, ALL recovered rapidly compared to AML (P < 0.001) and also the on the phase of treatment, i.e consolidation recovered earlier than induction (P < 0.001). There was no death recorded in this study population during febrile neutropenia. CONCLUSIONS: The incidence of febrile neutropenia depends upon the type of haematological malignancy and the aggressiveness of therapy required treating the disease especially during induction. The improvement in antimicrobial coverage and its prompt use leads to the selective growth of Gram‑positive organisms.

Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer.

CONTEXT: Rigosertib, a potent, multi-kinase inhibitor that selectively induces mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is being developed for the treatment of solid tumors and hematological malignancies. AIMS: To determine the safety, doselimiting toxicities, and clinical activity of rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or hematological malignancies; and to confirm the safety and tolerability of the recommended phase 2 dose (RPTD). SETTINGS AND DESIGN: Phase 1, open-label, dose-escalation study in men and women ≥18 years of age. MATERIALS AND METHODS: An escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase confirmed the maximum tolerated dose (MTD). STATISTICAL ANALYSIS USED: All data summaries were descriptive. PK parameters were estimated using compartmental analysis. RESULTS: 25 patients (16 male, 9 female, 26- 66 years, all Asian) were treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase. MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours was declared to be the RPTD. Best response was stable disease in 5 of 14 evaluable patients, with a mean (range) of 90 (43-108) days. CONCLUSIONS: 2400 mg rigosertib as a 4-hour infusion was identified as the RPTD. Five patients achieved stable disease lasting 6-16 weeks.

Myelomatous pleural effusion.

Serous effusions in multiple myeloma are uncommon but a myelomatous pleural effusion occurring in these patients is extremely rare. Here we report a rare case of a 38 years lady who was diagnosed to have multiple myeloma and subsequently developed pleural effusion. The myelomatous nature of the effusion was first diagnosed on cytology and subsequently confirmed by a pleural biopsy. The pleural effusion showed an initial response to chemotherapy but subsequently recurred.

Safe and efficacious use of procedural sedation and analgesia by non-anesthesiologists in a pediatric hematology-oncology unit.

BACKGROUND: Children often require relief of pain and anxiety while undergoing diagnostic and therapeutic procedures. Procedural sedation and analgesia (PSA) is the safe and effective control of pain, anxiety and motion so as to allow a necessary procedure to be performed and to provide an appropriate degree of memory loss or decreased awareness. OBJECTIVE: To prospectively describe procedural sedation and analgesia as performed in the pediatric oncology unit and to report the success of sedation and the incidence of complications. METHODS: IV Midazolam and IV Ketamine were used for PSA in pediatric oncology patients undergoing painful procedures. RESULTS: Between June 2004 and December 2004, 55 diagnostic and therapeutic procedures were performed using PSA in 16 children. There were 9 boys and 7 girls with a median age of 11 years. Twelve patients had hematolymphoid malignancies and 4 patients had solid tumors. The indication for PSA were bone marrow aspiration and or biopsy in 7 patients, therapeutic lumbar puncture in 43 patients, bone marrow aspiration and lumbar puncture in 4 patients and skin biopsy in 1 patient. All 55 procedures were successfully completed. Adverse events occurred in 15 (27%) episodes and included transient drop in oxygen saturation, vomiting, dizziness and disinhibition with crying spells. Average time to arousable state and full recovery was 22 minutes and 31 minutes respectively. None of the patients complained of post procedure pain nor recalled the procedure at the follow up visit. CONCLUSION: Procedural sedation and analgesia using midazolam and ketamine is a safe and efficient method of limiting anxiety and procedure related pain and can be successfully administered by non-anaesthesiologists. The complication rate is low and can be easily managed.

Impaired cell motility in chronic myeloid leukemic granulocytes related to altered cytoskeletal pattern.

The bactericidal activity of polymorphonuclear leucocyte (PMNL) against infection stimulates cytoskeletal changes accompanied with alteration in adhesion and locomotion. Microfilaments, the motile apparatus is known to regulate these changes by polymerization of monomeric G-actin to fibrous F-actin. PMNL from chronic myeloid leukemia (CML) patients have been reported to be defective in locomotion in response to synthetic peptide, n-formyl-methionyl-leucyl-phenylalanine (fMLP) but the mechanism leading to defective locomotion and their spatial reorganization remains unclear. Therefore, in order to study the cause of defective motility of PMNL from CML patients the spatial distribution and reorganization of microfilaments and microtubules in response to fMLP have been examined by transmission electron (TEM) and scanning electron microscopy (SEM). Under SEM, the PMNL-CML surface appeared smoother with reduced ruffling resulting in rounding off cells with lesser polarized morphology. Unstimulated PMNL from normal as well as CML subjects showed shorter and fewer microtubules and evenly distributed microfilaments as compared to fMLP stimulated PMNL. It is proposed that the cause of defective locomotion was due to reduced surface activity as a consequence of altered cytoskeletal configuration. This phenomenon seems to be related to impaired functional appendages and as a whole led to the defective cell motility and hence reduced chemotaxis in PMNL from CML patients.

Cumulative risk and trends in prostate cancer incidence in Mumbai, India.

BACKGROUND: Information relating to cancer incidence trends in a community forms the scientific basis for the planning and organization of prevention, diagnosis and treatment of cancer. We here estimated the cumulative risk and trends in incidence of prostate cancer in Mumbai, India, using data collected by the Bombay Population-based Cancer Registry from the year 1986 to 2000. METHODS: During the 15 year period, a total of 2864 prostate cancer cases (4.7% of all male cancers and 2.4% of all cancers) were registered by the Bombay Population-based Cancer Registry. For evaluation of the trend, we applied a linear regression model based on the logarithm of the observed incidence rates. The annual percentage changes were also computed for the evaluation. Cumulative incidence rates percentages were calculated by adding up the age specific incidence rates at single ages and then expressed as a percentage. RESULTS: Analysis of the trends in age-adjusted incidence rates of prostate cancer during the period 1986 to 2000 showed no statistically significant increase or decrease and the rates proved stable across the various age groups (00-49, 50-69 and 70+) also. The probability estimates indicated that one out of every 59 men will contract a prostate cancer at some time in his whole life and 99% of the chance is after he reaches the age of 50. CONCLUSION: The stability in age adjusted-incidence rates indicates that there are no changes in the etiological factors for prostate cancer in Mumbai, India. These findings may be of general interest because changes in diagnostic practices are confounded in the time trends of prostate cancer change in many western countries preventing inferences on the changes in risk.

Oral cancers in Mumbai, India: a fifteen years perspective with respect to incidence trend and cumulative risk.

OBJECTIVE: We estimated the time trends in the incidence and the risk of developing an oral cancer in Mumbai, Indian population using the data collected by the Bombay Population Based Cancer Registry during the 15 year period from 1986 to 2000. METHODS: A total of 9,670 oral cancers (8.2% of all neoplasms) were registered, of which 6577 were in males and 3093 in females (10.7% and 5.4% of the respective totals for the two genders). For evaluation of the trend, we applied a linear regression model based on the logarithm of the observed incidence rates. The annual percentage changes were also computed for the incidence rates to evaluate the time trend. RESULTS: In males, a statistically significant decreasing trend in the overall age-adjusted incidence rates were observed during the period 1986 to 2000, with an yearly decrease of 1.70%. This decrease was significant for men above the age of 40, but for young adult men below the age of 40, there was no significant decrease, the level being stable. In females, the overall decreasing trend in the age-adjusted incidence rates of oral cancers was not significant, but in the age group 40-59, a significant decline was observed. The probability estimates indicated that one out of every 57 men and one out of every 95 women will contract any oral cancer at some time in their whole life and 97% of the chance is after he or she completes the age of 40. CONCLUSION: The observed decreasing trend in oral cancers in Indian men may be attributed to a decrease in the usage of pan and tobacco. The high prevalence of the usage of smokeless tobacco among young adult men and women may explain the stable trend in oral cancer incidence in this group. These findings help to strengthen the association between tobacco use and oral cancer risk.

Imatinib in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of gastrointestinal tract. The tumors express the cell surface transmembrane receptor KIT that has a tyrosine kinase activity and is a protein product of KIT protoeoncogene. These tumors occur in the whole of Gastrointestinal tract. Treatment includes surgical resection for localized tumors. For metastatic disease treatment options include systemic chemotherapy, radiation therapy, with a response rate of less than 10%. Presently Imatinib; a tyrosine kinase inhibitor has shown promising result with response rates upto 59-69% in phase II results in metastatic setting; and ongoing phase II & phase III trials in adjuvant setting will help to establish its role as an adjuvant to surgery. We have treated eleven patients of metastatic GIST with Imatinib and we hereby present these cases.

Decreasing trend in the incidence of stomach cancer in Mumbai, India, during 1988 to 1999.

The time trend in incidence of stomach cancer in males and females in Mumbai, India during 1988 to 1999 was estimated using data collected by the Bombay Population-based Cancer Registry. During the 12-year period, a total of 3657 stomach cancer cases (3.9% of all cancers) were registered by the Bombay Population-based Cancer Registry of which 2467 (5.1% of all male cancers) were in males and 1184 (2.6% of all female cancers) in females. For evaluation of the trend, we applied a linear regression model based on the logarithm of the observed incidence rates. The annual percentage changes were also computed for the incidence rates for evaluating the time trend. A statistically significant decreasing trend in the overall age-adjusted incidence rates of stomach cancer was observed during the period 1988 to 1999, with an yearly decrease of 4.44% in males and 2.56% in females. This decrease was most striking in males in the age groups 40-59 and 60+, and in females only in the age group 40-59. The probability estimates indicated that one out of every 92 men and one out of every 187 women will contract a stomach cancer at some time in their whole life and 95% of the chance is after his or her 40th birthday. The decreasing trend in the age-adjusted incidence rates of stomach cancer in both the sexes indicates that there is a critical change in the etiology of this cancer. The findings may provide clues relating to various life-style and environmental changes impacting on stomach cancer incidence.

Hypercalcemia induced by parathyroid hormone-related peptide after treatment of squamous cell carcinoma of oral cavity.

Squamous cell carcinoma of the head and neck is a rare cause of humoral hypercalcemia of malignancy. This paraneoplastic syndrome is usually one of the presenting symptoms of the disease. We report a case of squamous cell carcinoma of the oral cavity that presumably elaborated parathyroid hormone-related peptide (PTH-rP) and caused hypercalcemia only after radiotherapy and chemotherapy.

Benign multilocular cystic nephroma.

This article reports a case of cystic nephroma to bring awareness about the benign nature of this condition. The patient presented with a painless abdominal mass. Computed tomography showed a homogeneous, multicystic tumor of the superolateral portion of the left kidney with thin septa without solid parts. Histology confirmed the diagnosis of cystic nephroma.

Leukemia in infants.

OBJECTIVE: Acute Leukemia is rare in infants. It is characterized by non-specific symptomatology requiring a high index of suspicion on the part of a pediatrician for referral and diagnosis. It has peculiar biological features, unresponsiveness to treatment and poor prognosis. METHODS: Eighteen infants with acute leukemia were seen during 1994 to 2001 and were analyzed on the basis of clinical and laboratory data. There were 13 cases of Acute Lymphoblastic Leukemia (ALL), 4 cases of Acute Myeloid Leukemia (AML) and one case remained unclassifiable, as the surface markers could not be done. Morphologically 9/13 cases of ALL were of FAB L1 type and remaining of L2 subtype, and 2/4 cases of AML were of FAB M1 type and remaining of M2 subtype. RESULT: Clinical data was available completely only in 11 cases. Hyperleucocytosis was present in 4 cases, organomegaly in 8 cases and lympadenopathy in 5 cases. One patient presented with a chloroma in the retrorbital region although there was no parenchymal involvement of the brain. Immunophenotyping could be done in 13 cases, where 7 cases were diagnosed as CALLA positive-ALL (HLADR+, CD19+, CD10+), 2 cases as Early Pre-B ALL (HLADR+, CD19+, CD10 negative), one as T ALL (cCD3+, CD2+, CD7+) and 3 cases as AML (CD13+, CD33+, HLADR+). None of our patients received treatment.

2-CdA in the treatment of hairy cell leukaemia.

INTRODUCTION: Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder. Treatment options available are splenectomy, interferon, DCF and 2-CdA. 2-CdA is considered to have curative potential as proved by the other studies. METHODS: We gave 2-CdA in a dose of 0.09/kg/day as a continuous infusion in sixteen patients of hairy cell leukaemia. RESULTS: Three patients developed neutropenia post transfusion. At the end of three months all patients were in remission. Two patients relapsed at the median follow-up of 15 months. CONCLUSION: 2-CdA in HCL can achieve complete remission, prolonged survival and care as well.

Hydroxyurea induced leg ulcers.

A 34 years non diabetic lady with chronic myeloid leukaemia (CML) was treated with hydroxyurea and interferon. She developed leg ulcers. First time on left toe and three months later on right foot, a rare complication of hydroxyurea. Both were treated with local wound care and antibiotics. First time dose of hydroxyurea was reduced and second time drug was discontinued.

Results of allogeneic bone marrow transplant in chronic myeloid leukaemia following conditioning with busulfan and cyclophosphamide.

OBJECTIVE: To study the outcome of oral busulfan and intravenous cyclophosphamide (BuCY 2 regimen) followed by allogeneic bone marrow transplant (BMT) in a cohort of patients with Philadelphia chromosome (Ph+) chronic myeloid leukaemia (CML) in a single centre. METHODS: From 1991 to March 1998, a total of 27 consecutive Ph+ CML patients received busulfan 4 mg/kg/day over 4 days and cyclophosphamide 60 mg/kg/day over 2 days followed by infusion of HLA-identical sibling haematopoietic stem cells. All except one (who received peripheral blood stem cells) were given donor bone marrow cells. Post-transplant graft versus host disease (GVHD) prophylaxis included a short course of methotrexate (on days +1, +3, +6 and +11) and cyclosporine till day +180. RESULTS: With a median follow-up of 30.5 months (1-55+ months), 14 patients (52%) are alive free from relapse. Early mortality was relatively high with 10 patients (37%) dying within first 100 days post-transplant. Acute GVHD developed in 14 patients (52%) inspite of GVHD prophylaxis with methotrexate and cyclosporine; six had grade I/II and eight grade III/IV. Chronic GVHD developed in five of 15 patients who lived beyond 70 days. CONCLUSION: Allogeneic BMT appears to result in eradication of CML and ensure disease free survival in about half of the young patients. However, efforts should be on to minimise early mortality.

Hairy cell leukemia--results with alpha interferon therapy.

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder. Although now multiple treatment options are being available, the optimal treatment of this disease still remains debatable. Inspite of the advent of newer purine analogues, in India recombinant interferon is the only freely available first line treatment. We report our experience of long term remissions in HCL with interferon alpha 2a. Of a total of 35 cases of HCL we were able to treat 19 cases with interferon. Of 18 evaluable cases an overall response of 88.9% was achieved. With a median follow up of 31 months a disease free survival was 83%. Thus with a dose of 3 million units s.c. daily for 6 months at least, we feel that a reasonably good long term remission can be obtained. The cost of the treatment however, is still a deterrent.

Descriptive epidemiology of leukaemias in Greater Mumbai.

BACKGROUND: There is little data available on the occurrence of leukaemias in India. This is despite a large number of patients being diagnosed and treated at various cancer centres all over the country. We, therefore, analysed the available data of the Bombay Cancer Registry to ascertain the epidemiological characteristics of leukaemias in India. METHODS: The incidence and mortality rates of leukaemias by cell type and sex were obtained for the most recent 5 years (1989-93). The data of the past 30 years were used to study the time trends using a linear regression model based on the logarithms of the incidence rates. RESULTS: Leukaemias constituted 3.9% of all registered cancer cases and 5.4% of all registered deaths in Greater Mumbai. Males were affected more frequently than females. Myeloid leukaemias were the commonest. A bimodal age incidence was observed with the first peak in childhood, a trough between 15 to 19 years of age and a slow rise thereafter. Among the various religious groups Hindus had the highest rate. An increasing trend in the incidence of all types of leukaemias was also observed. CONCLUSION: The incidence of leukaemias in Greater Mumbai is comparable to world rates. There is a male preponderance in all cell types and an increase in incidence was observed over the last 30 years. The higher incidence of myeloid leukaemias observed by us might be related to under-reporting of chronic lymphatic leukaemia.